Obesity is the risk factor for various adult diseases that are represented by hypertension, diabetes, hyperlipemia, ischemic heart disease, and others. Since many of them are chronic disorders, they are believed to cause an escalation in the medical cost in the future and are becoming a big social problem.
Adequate examination and identification of such obesity condition is indispensable to the proper treatment that follows. Hence, there has always been a need to uncover convenient and highly accurate obesity markers. In recent years, it has also been beginning to be recognized that the genotype, such as genetic polymorphism, of a recipient of a drug influences the efficacy of the administered drug. Markers for examination or diagnosis at molecular levels have been desired in the clinical tests at the development stages of drugs or in the so-called tailored medication.
Under these circumstances BMI (Body Mass Index: body weight (kg)/height (m)/height (m)) is principally used as a maker for obesity. The present situation is thus such that there are hardly known any markers capable of diagnosis at molecular levels such as gene or protein.
MCP-1 is a protein whose open reading frame consist of 99 amino acids (in the case of human) and which belongs to the CC chemokine subfamily (Accession No. human NM002982 (SEQ ID NO:9 and NO:10)), murine NM011333 (SEQ ID NO:11 and NO:12)). MCP-1 was cloned in 1989 (Yoshimura T. et al., FEBS Letters, 244, 487-493 (1989); Furutani Y. et al., Biochem. Biophys. Res. Commun., 159, 249-255 (1989)) and was later implicated to be related with arteriosclerosis, rheumatoid arthritis and nephritis (Proc. Natl. Acad. Sci. USA, 87, 5134-5138 (1990); J. Clin. Invest. 90, 772-779 (1992); Kidney Int. 44, 1036-1047 (1993)).
Chemokines are a group of proteins having migration activity toward leukocytes. It has become clear that they are involved in the pathological onset, progress, and animus of inflammation at its acute and chronic stages. Particularly, it is known that MCP-1 possesses potent chemotaxis and activation action toward monocytes. It is, thus, thought that MCP-1 can be used in the utility of immunoactivation action, anti-tumor action and the like.
As stated above, a number of findings on MCP-1 have been reported, and it is known that MCP-1 is responsible for diverse life phenomena in the living body. However, concerning the relationship between MCP-1 and obesity, there were only a report that the expression level of MCP-1 was elevated when leptin, which was known as a satiety factor, was administered to certain cells (FASEB J., 13, 1231-1238 (1999); J. Biol. Chem., 276, 25096-25100 (2001)) and a report suggesting that the stimulation by chemokines was indirectly involved in the accumulation of fat (Molecular and cellular Endocrin., 175, 81-92 (2001)). The direct relationship between MCP-1 and obesity as well as the correlation between the expression level of MCP-1 and obesity or body weight changes has not been known at all.